This proposal addresses the continuation of our efforts aimed at the development of mild, stereocontrolled, and enantioselective methodology for the construction of five-membered-ring compounds. The technique has as its ultimate goal annulations leading to cyclopentenes, dihydrofurans, and pyrrolines, as these constitute subunits of many natural products of biological significance. It is based on either the [2+3] intermolecular addition of ester dienolate anions to carbonyl derivatives (for cyclopentenes and dihydrofurans) or the [4+1] intramolecular addition of azides to dienes (for pyrrolines). The most important development addressed in this project will be the detailed investigation of annulations of enones and aldehydes with the dienolate derived from 4- silyloxybromocrotonate. The silicon-mediated rearrangements of vinylcyclopropanes and vinyloxiranes to cyclopentenes and dihydrofurans hold the potential of providing on of the mildest annulation procedures to date. The project will be guided along the following major aims: a. Development of nucleophilic or radical alternatives to the ring opening of vinylcyclopropanes and vinyloxiranes. b. Detailed investigation of the stereochemical course of the additions of dienolate anions derived from 2- bromocrotonates to aldehydes and enones in order to understand the diastereoselectivity of this process. c. Investigation of fluoride- catalyzed rearrangements of silyl-enol-ether-terminated vinyl-cyclopropanes and vinyl-oxiranes and insight into mechanistic details of this process. d. Investigations of enantioselective synthesis of vinyloxiranes and vinylcyclopropanes either by a chiral-auxillary approach (reagent control or by additions of the above dienolates to chiral precursors (substrate control). e. Investigation of possible chirality transfer from rigid chiral silicon auxiliaries. f. Applications of these methodologies to the preparation of specionin (an antifeedant substance), pyrrolizidine and indolizidine alkaloids of known antibiotic or antiviral activities, and the furanoid subunits that are integral parts of many antibiotics; and to the second generation synthesis of retigeranic acid. The direction of research during the next funding period is aimed at the conclusion of investigations that are necessary in order to render the [2+3] asymmetric annulation methodology a permanent tool in the field of carbocylic and heterocylic synthesis. Reliable provision of cyclopentanoid, furanoid, and pyrroline units extends the applications of this methodology to the design of heterocyclic natural products of biological significance.